Optimizing the Sintering Conditions of (Fe,Co)1.95(P,Si) Compounds for Permanent Magnet Applications.

(Fe,Co)2(P,Si) quaternary compounds combine large uniaxial magnetocrystalline anisotropy, significant saturation magnetization and tunable Curie temperature, making them attractive for permanent magnet applications. Single crystals or conventionally prepared bulk polycrystalline (Fe,Co)2(P,Si) samples do not, however, show a significant coercivity. Here, after a ball-milling stage of elemental precursors, we optimize the sintering temperature and duration during the solid-state synthesis of bulk Fe1.85Co0.1P0.8Si0.2 compounds so as to obtain coercivity in bulk samples. We pay special attention to shortening the heat treatment in order to limit grain growth. Powder X-ray diffraction experiments demonstrate that a sintering of a few minutes is sufficient to form the desired Fe2P-type hexagonal structure with limited secondary-phase content (~5 wt.%). Coercivity is achieved in bulk Fe1.85Co0.1P0.8Si0.2 quaternary compounds by shortening the heat treatment. Surprisingly, the largest coercivities are observed in the samples presenting large amounts of secondary-phase content (>5 wt.%). In addition to the shape of the virgin magnetization curve, this may indicate a dominant wall-pining coercivity mechanism. Despite a tenfold improvement of the coercive fields for bulk samples, the achieved performances remain modest (HC ≈ 0.6 kOe at room temperature). These results nonetheless establish a benchmark for future developments of (Fe,Co)2(P,Si) compounds as permanent magnets.

The Ability of Clinically Relevant Chemotherapeutics to Induce Immunogenic Cell Death in Squamous Cell Carcinoma.

BACKGROUND: Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC. METHODS: We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP), Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients. RESULTS: Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro, it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells. CONCLUSION: The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.

E3 ubiquitin ligase TRIM21 targets TIF1γ to regulate ß-catenin signaling in glioblastoma.

Background: Elucidation of the mechanism of ubiquitation has led to novel ways to treat glioblastoma (GBM). A tripartite motif (TRIM) protein mediates a reversible, stringent ubiquitation which is closely related to glioma malignancy. This study intends to screen the most vital and abnormal regulating component of the tripartite motif protein and to explore its underlying mechanisms. Methods: TRIM21 is identified as an important oncogene that accelerates the progression of glioma cell through database in a multidimensional way and this is confirmed in human samples and cells. Tandem Mass Tags (TMT) and MS analysis are performed to discover the substrates of TRIM21.The underlying mechanisms are further investigated by CO-IP, luciferase reporter assays and gain and loss of function assays. In vivo treatment with siRNA is applied to evaluate the therapeutic significance of TRIM21. Result: We screened a panel of TRIM proteins and identified TRIM21, a E3 ubiquitin-protein ligase and autoantigen, as well as a prognostic biomarker for GBM. Functionally, high expression of wild-type TRIM21 accelerates tumor progression in vitro and in vivo, whereas TRIM21 mutants, including one with a critical RING-finger deletion, do not. Mechanistically, TRIM21 stimulates K63-linked ubiquitination and subcellular translocation of active ß-catenin from the cytoplasm to the nucleus. Moreover, TRIM21 forms a complex with the ß-catenin upstream regulator, TIF1γ, in the nucleus and accelerated its degradation by inducing K48-linked ubiquitination at K5 site, consequently increasing further nuclear ß-catenin presence. Endogenous TRIM21 levels are found to be inversely correlated with TIF1γ but positively correlated with ß-catenin in glioma tissue microarray experiments. Furthermore, direct injection of TRIM21 small interfering RNA (siRNA) into U87 cell-derived tumors (in vivo treatment with siRNA) is proved to inhibit tumor growth in nude mice. Conclusion: This work suggests that TRIM21/TIF1γ/ß-catenin axis is involved in the progression of human GBM. TRIM21 is a promising therapeutic and prognostic biomarker for glioma with hyperactive ß-catenin.